ChemPath 3: Sodium and Fluid Balance

Question 1

Define Hyponatraemia

Answer 1

• Serum sodium <135 mmol/L

Question 2

Which is the commonest electrolyte abnormality in hospitalised patients?

Answer 2

Hyponatraemia

Question 3

Which hormone regulates water balance?

Answer 3

ADH

Question 4

Outline how ADH works

Answer 4

1. Synthesised in hypothalamus
2. Secreted from posterior pituitary, acts on CD in the kidney
3. Water retention through insertion of aquaporin 2 (AQA2)

Question 5

Briefly explain the pathogenesis of hyponatraemia

Answer 5

Question 6

Which receptors does ADH act on?

What happens once it has bound to these receptors?

Answer 6

V2 receptors in collecting duct –> insertion of AQA2

Question 7

Where are V1 receptors found?

Answer 7

1. Vascular smooth muscle
2. Vasoconstriction – higher concentrations
3. “Vasopressin”

Question 8

What are the 2 main stimuli for ADH secretion?

Answer 8

1. Serum osmolality (high) – mediated by hypothalamic osmoreceptors
2. Blood volume/pressure (low) – mediated by baroreceptors in carotids, atria, aorta

Question 9

What is the effect of increased ADH secretion on serum sodium?

Answer 9

1. ADH only resorbs water, not any sodium
2. –> Hyponatraemia

Question 10

What is the first step in clinical assessment of a patient with hyponatraemia?

Answer 10

clinical assessment of volume status (Hypovolaemia, euvolemia, hypervolaemia)

Question 11

What are the clinical signs of hypovolaemia?

Answer 11

• Tachycardia
• Postural hypotension
• Dry mucous membranes
• Reduced skin turgor
• Confusion or drowsiness
• Reduced urine output
• Low urine Na+ (<20)

Question 12

What is the normal range of urine Na?

Answer 12

• Normal range = 40-220 mEq/L [<20 non-renal loss; >20 in renal loss)

Question 13

What is the issue with using urine Na as a tool for assessing ?hyponatraemia?

Answer 13

• Patients on diuretics may have urine Na that is not reliable (hypovolemic, but no hyponatraemia)

Question 14

What are the clinical Signs of hypervolemia?

Answer 14

• Raised JVP
• Bi-basal crackles
• Peripheral oedema

Question 15

What does hyponatraemia in a hypovolaemic patient require?

Answer 15

requires more sodium than water loss

Question 16

What are the causes of hyponatraemia in a hypovolaemic patient?

Answer 16

• Diuretics
• Diarrhoea and vomiting

Question 17

What is the difference between hypovolemic Hyponatraemia and dehydration?

Answer 17

• Hypovolemic Hyponatraemia = loss of water and sodium (as opposed to dehydration = loss of just water)

Question 18

What is the pathophysiology of hypovolemic hyponatraemia?

Answer 18

• Start euvolaemia and then a hypovolemia develops (quickly)
• –> release of ADH à just water retention
• –> dilutes [Na+] but not to same volume status as they were when euvolaemic
• –> hyponatraemia + hypovolaemic

Question 19

What are the causes of hyponatraemia in a hypervolemic patient?

Answer 19

• excess water,
• excess ADH
• Cardiac failure → low pressure → detected by baroreceptors → ADH release
• Cirrhosis → vasodilated due to excess NO → low BP → baroreceptors → ADH release
• Renal failure → not excreting enough water

Question 20

What are the causes of hyponatraemia in euvolemic patient?

Answer 20

• Hypothyroidism à reduced contractility à reduced BP à ADH release
• Adrenal insufficiency à less aldosterone à less Na⁺ reabsorption
• SIADH –> AQA2 water retention –> inc. volume –> suppress RAAS –> less aldosterone –> less Na⁺ reabsorption
  
  • CNS pathology – stroke, haemorrhage, tumour
  • Lung pathology – pneumonia (Legionella), pneumothorax
  • Drugs – SSRI, TCA, PPI, carbamazepine, opiates
  • Tumours
  • Surgery

Question 21

• What investigations would you order in a patient with euvolemic hyponatraemia?

Answer 21

• Hypothyroidism → thyroid function tests
• Adrenal insufficiency → short SynACTHen test
• SIADH → plasma and urine osmolality → low plasma and high urine osmolality
  
  • Excess ADH = excess water = volume expansion → secretion for BNP → naturesis à euvolaemic
  • If sodium is high**, it’s a **pseudohyponatraemia (i.e. hyperlipidaemia, hyperproteinaemia)

Question 22

What is required for the diagnosis of SIADH?

Answer 22

• No hypovolaemia (euvolaemia)
• No hypothyroidism
• No adrenal insufficiency
• Reduced plasma osmolality (resorbing lots of water) AND
• Increased urine osmolality (>100) (concentrating the urine) – need to know this ref range

Question 23

What is the management of hypovolemic patient with hyponatraemia

Answer 23

volume replacement with 0.9% saline

Question 24

What is the Management of euvolaemic patient with hyponatraemia

Answer 24

fluid restrict (<750ml/day + ABx infusions) + treat underlying cause

Question 25

What is the Management of hypervolemic patient with hyponatraemia

Answer 25

**fluid restrict** (\<750ml/day + ABx infusions) + **treat** **underlying cause**

Question 26

What are the signs of severe hyponatraemia?

Answer 26

* Reduced GCS * Seizures

Question 27

What is the Tx for severe hyponatraemia?

Answer 27

* Seek expert help – _treat with hypertonic 3% saline_

Question 28

What is the complication that arises from too rapid a correction of hyponatraemia?

Answer 28

**Central pontine myelinolysis** * a neurological condition involving severe damage to the myelin sheath of nerve cells in the pons

Question 29

What are the signs and symptoms of Central Pontine Myelinolysis?

Answer 29

* Quadriplegia, dysarthria, dysphagia, seizures, coma, death

Question 30

What rate should hyponatraemia be corrected at?

Answer 30

not greater than 8-10mmol/L in the first 24 hours

Question 31

Which drug is used to Tx SIADH if fluid restriction is not enough?

Answer 31

* **Demeclocycline** --\> induce nephrogenic diabetes insipidus * **Tolvaptan** – V2 receptor antagonist

Question 32

How does Demeclocycline work?

Answer 32

* Reduces responsiveness of collecting tubule cells to ADH * Monitor U&Es as risk of **nephrotoxicity**

Question 33

Define hypernatraemia

Answer 33

* Serum [Na+] \> 145mmol/L

Question 34

What are the main causes of hypernatremia?

Answer 34

* **1^st** --\> increase sodium intake **AND/OR** have a loss of water: * **Increase in sodium:** * _Medical_ high intake (hypertonic saline, sodium bicarbonate) * _Dietary_ high intake (salty infant formula, high dietary salt) * **Conn’s syndrome** (high aldosterone: renin ratio), **BAH** (high aldosterone: renin ratio) * **Renal artery stenosis** (low GFR from RAS à low BP at JGA à high renin à high aldosterone) * **Cushing’s syndrome** (overactivation of MR by cortisol à aldosterone-like effect) * **Loss of water:** * **Renal losses:** * Osmotic diuresis * **Diabetes insipidus** (less ADH action / release) * **Insensitivity/lack to/of ADH** à solitary water losses à hypovolaemia * Body compensates by **resorbing more Na⁺** to reduce the water loss * Water loss persists and so you get a hypovolaemic hypernatraemia * **Non-renal losses:** * GI loss * sweat loss * 2**^nd** --\> maintain the low water intake: * Child / elderly / dementia * Fasting for surgery * Simply cannot keep up with losses * Busy nightshift and forget to drink

Question 35

What are the investigations for patient with suspected diabetes insipidus?

Answer 35

* Serum glucose – exclude diabetes mellitus --\> osmotic diuresis * Serum potassium – exclude hypokalaemia --\> nephrogenic DI * Serum calcium – exclude hypercalcaemia --\> nephrogenic DI * Plasma and urine osmolality –\> exclude hyperaldosteronism (high plasma osmolality, low urine osmolality) * Water deprivation test (normal = concentrated urine, no ADH = carry on passing water – dilute urine)

Question 36

What is the management of hypernatraemia?

Answer 36

* Fluid replacement → dextrose (if the patient is also hypovolemic, then 0.9% saline and 5% dextrose water) * Treat underlying cause i.e. * Correct water deficit → **5% dextrose** * Correct ECF volume depletion → **0.9% saline** * Serial Na+ measurements → **every 4-6 hours**

Question 37

What are the effects of **diabetes mellitus** on serum sodium?

Answer 37

* Variable * Hyperglycaemia draws water out of cells leading to hyponatraemia * Osmotic diuresis in uncontrolled diabetes leads to loss of water and hypernatremia